Assessing tolerability with the Functional Assessment of Cancer Therapy item GP5: psychometric evidence from LIBRETTO-531, a phase 3 trial of selpercatinib in medullary thyroid cancer.

Background: This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing "high side-effect burden" using a rating of 3 or 4 (score ranges 0-4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC).

Methodology: Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline.

The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits.

Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits.

Real-world clinical and economic outcomes for daily teriparatide patients in Japan.

A large medical and pharmacy claims database was used to evaluate outcomes in daily teriparatide (D-TPD) patients in Japan. 445 patients were identified (April 2008-July 2013) with 6+ months' pre- and 18+ months' post-index observation. D-TPD 20 µg subcutaneous injection is indicated for individuals at high risk of fracture.

CNVs conferring risk of autism or schizophrenia affect cognition in controls.

In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease.

Analysis and perspective of Dosing accuracy and insulin flow rate characteristics of a new disposable insulin pen, FlexTouch, compared with SoloSTAR.

Pen injectors for the administration of insulin have been available since the 1980s. The first insulin pen, NovoPen®, was introduced by Novo in 1985 (http://www.novonordisk.

Genetic variation in metabolizing enzyme and transporter genes: comprehensive assessment in 3 major East Asian subpopulations with comparison to Caucasians and Africans.

The advent of high-throughput technologies has proven valuable in the assessment of genetic differences and their effects on drug activation, metabolism, disposition, and transport. However, most studies to date have focused on a small number of genes or few alleles, some of which are rare and therefore observed infrequently or lacked rigorous ethnic characterization, thus reducing the ability to extrapolate within and among populations. In this study, the authors comprehensively assessed the allele frequencies of 165 variants comprising 27 drug-metabolizing enzyme and transporter (DMET) genes from 2188 participants across 3 major ethnic populations: Caucasians, Africans, and East Asians.

Effects of duloxetine on the pharmacodynamics and pharmacokinetics of warfarin at steady state in healthy subjects.

This study evaluated the pharmacodynamics and pharmacokinetics of once-daily dosing of warfarin at steady state when taken concomitantly with once-daily doses of duloxetine. Healthy subjects with a stable international normalized ratio (INR) of 1.5 to 2.

Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel.

Prasugrel and clopidogrel, thienopyridine prodrugs, are each metabolized to an active metabolite that inhibits the platelet P2Y(12) ADP receptor. In this open-label, 4-period crossover study, the effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel were assessed in healthy subjects given single doses of prasugrel 60 mg and clopidogrel 300 mg with and without concurrent lansoprazole 30 mg qd. C(max) and AUC(0-tlast) of prasugrel's active metabolite, R-138727, and clopidogrel's inactive carboxylic acid metabolite, SR26334, were assessed.

Binary regression with misclassified response and covariate subject to measurement error: a bayesian approach.

We consider a Bayesian analysis for modeling a binary response that is subject to misclassification. Additionally, an explanatory variable is assumed to be unobservable, but measurements are available on its surrogate. A binary regression model is developed to incorporate the measurement error in the covariate as well as the misclassification in the response.

Safety, tolerability, QTc evaluation, and pharmacokinetics of single and multiple doses of enzastaurin HCl (LY317615), a protein kinase C-beta inhibitor, in healthy subjects.

The safety, tolerability, and pharmacokinetics of orally administered enzastaurin were evaluated in 2 placebo-controlled, dose escalation studies in healthy subjects. In the first human dose study, single doses (2-400 mg) were evaluated, with 22 subjects receiving enzastaurin. The mean half-lives of enzastaurin and its metabolites ranged from approximately 12 to 40 hours.

Does treatment with duloxetine for neuropathic pain impact glycemic control?

Objective: We examined changes in metabolic parameters in clinical trials of duloxetine for diabetic peripheral neuropathic pain (DPNP).

Research Design And Methods: Data were pooled from three similarly designed clinical trials. Adults with diabetes and DPNP (n = 1,024) were randomized to 60 mg duloxetine q.

Metabotropic glutamate receptors as novel targets for anxiety and stress disorders.

Anxiety and stress disorders are the most commonly occurring of all mental illnesses, and current treatments are less than satisfactory. So, the discovery of novel approaches to treat anxiety disorders remains an important area of neuroscience research. Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system, and G-protein-coupled metabotropic glutamate (mGlu) receptors function to regulate excitability via pre- and postsynaptic mechanisms.

Effects of intramuscular olanzapine vs. haloperidol and placebo on QTc intervals in acutely agitated patients.

Prolongation of the QTc interval has been reported during treatment with oral antipsychotic agents and may be more pronounced during parenteral administration. Pooled QTc interval data from acutely agitated patients across four double-blind trials were compared. Databases included: placebo-controlled [two schizophrenia, one bipolar mania trials (n=565)]; haloperidol-controlled [two schizophrenia trials (n=482)]; geriatric placebo-controlled [1 dementia trial (n=204)].

Safety profile of atomoxetine in the treatment of children and adolescents with ADHD.

Atomoxetine is a selective norepinephrine reuptake inhibitor that is being developed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine will be the first nonstimulant medication approved by the U.S.

AKT-1, -2, and -3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon.

Purpose: The AKT/PKB kinase controls many of the intracellular processes that are dysregulated in human cancer, including the suppression of apoptosis and anoikis and the induction of cell cycle progression. Three isoforms of AKT have been identified: AKT-1, -2, and -3. Selective up-regulation of AKT-3 RNA expression has been reported in hormone-independent breast and prostate cancer cell lines suggesting that AKT-3 expression may be increased with breast or prostate tumor progression.